Abstract
Introduction: This review explores angiogenesis, vascular dysfunction, the complement system, RAAS, apoptosis and NETosis as potential pathways that are dysregulated during preeclampsia, HIV infection and ART usage. Results: HIV-1 accessory and matrix proteins are protagonists for the elevation of oxidative stress, apoptosis, angiogenesis, and elevation of adhesion markers. Despite the immunodeficiency during HIV-1 infection, HIV-1 exploits our cellular defence arsenal by escaping cell-mediated lysis, yet HIV-1 infectivity is enhanced via C5a release of TNF-α and IL-6. This review demonstrates that PE is an oxidatively stressed microenvironment associated with increased apoptosis and NETosis, but with a decline in angiogenesis. Immune reconstitution in the duality of HIV-1 and PE by protease inhibitors, HAART and nucleoside reverse transcriptase, affect similar cellular pathways that eventuate in loss of endothelial cell integrity and, hence, its dysfunction. Conclusions: HIV-1 infection, preeclampsia and ARTs differentially affect endothelial cell function. In the synergy of both conditions, endothelial dysfunction predominates. This knowledge will help us to understand the effect of HIV infection and ART on immune reconstitution in preeclampsia.
Highlights
This review explores angiogenesis, vascular dysfunction, the complement system, Renin-Angiotensin-Aldosterone System (RAAS), apoptosis and NETosis as potential pathways that are dysregulated during preeclampsia, human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) usage
Because Neutrophil Extracellular Traps (NETs) are individually elevated in PE and HIV infections, it is surprisingly evident that NETs are suppressed in the co-infection of HIV-associated PE; this suppression may be attributed to ART usage [154]
This review explores research evidence that may aid in reducing the main direct and indirect (HIV infection) causes of global maternal mortality
Summary
Low and middle-income countries have higher maternal mortality rates (462 per 100,000 live births) compared to high-income countries (11 per 100,000 live births) [1]. A systematic analysis conducted by the World Health Organisation (WHO) indicates that haemorrhage and hypertensive disorders of pregnancy are the major causes of direct maternal deaths worldwide [1,2]. Preeclampsia (PE) is a hypertensive disorder of pregnancy and one of the main direct causes of maternal morbidity and mortality, whereas human immunodeficiency virus (HIV) infection in pregnancy remains the leading indirect cause of maternal deaths [3]. The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with an increased risk of severe outcomes in pregnancy than the general population [12,13,14]. The SARS-CoV-2 infection superimposed on HIV-associated pregnancy is complex as both impact the inflammatory response and influence endothelial function [15,16]. Endothelial dysfunction induces the maternal syndrome of PE [16]
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